Variations in maternal behavior regulate the development of behavioral and endocrine responses to stress in the rat (see Lie et al., Science, 199; Caldji et al., 1998 PNAS in Appendix). Perhaps the pivotal finding is that maternal care in infancy regulates the development of central CRF systems which serve to activate behavioral, endocrine and autonomic responses to stress. Variations in maternal care in the infant rat also influences the development of neural systems, such as glucocorticoid and GABAa receptor systems, which provide an inhibitory tone over CRF synthesis and release. Thus, the offspring of mothers which exhibit a low level of maternal licking/grooming and arched-back nursing (Low LG-ABN) show increased CRF expression, and decreased glucocorticoid and GABAa receptor levels by comparison to the offspring of High LG-ABN mothers. The level of CRF mRNA expression in the PVNh of the adult offspring was significantly correlated with the level of both maternal licking/grooming and arched-back nursing during the first 10 days of life. Our preliminary data suggest that these effects provide an example of the behavioral transmission of traits from one generation to the next. The next question concerns the origins of these individual differences in maternal behavior. The primary goal here is to understand the neurobiological basis for the relationships that exist between environmental stimuli, individual differences in parental behavior and the development of behavioral and endocrine responses to stress. The hypothesis which drives this grant attempts to explain these environmental effects in terms of the development of neural systems underlying fearfulness as well as those which mediate parental care. The experiments proposed here are designed to address the three principal tenets of this hypothesis: 1) that individual differences in maternal behavior are inherited via a behavioral mode of transmission, 2) that variations in maternal care are associated with individual differences in neural systems that mediate the expression of both stress reactivity and maternal behavior, 3) that there is a functional relationship between the individual differences in stress reactivity and those in maternal care, and 4) that such individual differences are, in turn, functionally related to the level of environmental demand which confronts the animal (more stressful environments result in Low LG-ABN mothers and offspring that are more reactive to stress).